PCT International Publication Nos. WO 89/04829 and WO 93/09114, and U.S. Pat. No. 5,039,676 disclose substituted tetrahydrofuran azole and imidazole compounds having utility as antifungal agents. Dioxolanyl imidazole and triazole antifungal agents and related compounds are described in U.S. Pat. Nos. 4,619,931, 4,861,879, 4,735,942 and 4,791,111. A number of processes for the synthesis of these compounds are known.
For example, PCT International Publication No. WO93/09114 discloses a process for the synthesis of trisubstituted tetrahydrofuran azole antifungals by reacting a tosylate of the formula (I) ##STR3## wherein X is both F or both Cl or one X is F and the other is Cl, with a compound of the formula (II) ##STR4## wherein R" is alkyl, alkenyl, alkynyl cycloalkyl, etc. The synthesis of a compound of the formula (I) is described in PCT International Publication No. WO94/25452. WO93/09114 also describes the conversion of a compound of the formula ##STR5## wherein W represents ##STR6## to a compound of the formula ##STR7## which is subsequently N-alkylated to give a compound of the formula ##STR8## wherein R" is as defined above.
N-alkylation of the triazolone group as described in the prior art is inefficient, requiring a large excess of an expensive alkylating agent, typically an alkyl bromide, and results in a mixture of N-alkylated and O-alkylated triazolone products, necessitating laborious purification methods and giving low yields of the N-alkylated triazolone.